cAMP-mediated protein phosphorylation plays a key role in the intracellular response of eukaryotic cells to hormonal signals (1,2). In the laboratory of the present inventors, there has recently been suggested a possible extracellular function for PKA in rabbit blood (3). It was based on the observation that thrombin-activation of rabbit platelets causes them to release PKA (alongside with its co-substrate ATP (4)) which then specifically phosphorylates a plasma protein (M, 135000) in a cAMP-dependent process (3).
In view of the implications such a phosphorylation may have in hemostasis and thrombosis, there was a need to determine whether or not thrombin similarly releases PKA from human platelets and to identify the human plasma protein, if any, which constitutes the PKA target substrate.